The novel benzopyran class of selective cyclooxygenase-2 inhibitors. Part III: the three microdose candidates

…, M Graneto, J Talley, T Maziasz, J Masferrer…

Index: Wang, Jane L.; Aston, Karl; Limburg, David; Ludwig, Cindy; Hallinan, Ann E.; Koszyk, Francis; Hamper, Bruce; Brown, David; Graneto, Matthew; Talley, John; Maziasz, Timothy; Masferrer, Jaime; Carter, Jeffery Bioorganic and Medicinal Chemistry Letters, 2010 , vol. 20, # 23 p. 7164 - 7168

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Citation Number: 16

Abstract

In this manuscript, we report the discovery of the substituted 2-trifluoromethyl-2H- benzopyran-3-carboxylic acids as a novel series of potent and selective cyclooxygenase-2 (COX-2) inhibitors. We provide the structure–activity relationships, optimization of design, testing criteria, and human half-life data. The challenge of a surprisingly long half-life (t1/2= 360h) of the first clinical candidate 1 and human t1/2 had been difficult to predict based on ...